C-reactive protein (CRP) is a liver-derived acute phase reactant that is a clinical marker of inflammation associated with poor cancer prognosis. Elevated CRP levels are observed in many types of cancer and are associated with significantly increased risk of metastasis, suggesting that CRP could have pro-metastatic actions. Here, we reported that CRP promotes lung metastasis by dampening the anti-cancer capacity of pulmonary macrophages in breast cancer and melanoma. Deletion of CRP in mice inhibited lung metastasis of breast cancer and melanoma cells without significantly impacting tumor growth compared to wildtype mice. In addition, the lungs of CRP deficient mice were enriched for activated pulmonary macrophages, which could be reduced to the level of wildtype mice by systemic administration of human CRP. Mechanistically, CRP blocked the activation of pulmonary macrophages induced by commensal bacteria in a FcγR2B-dependent manner, thereby impairing macrophage-mediated immune surveillance to promote the formation of a pre-metastatic niche in the lungs of tumor-bearing mice. Accordingly, treatment with specific CRP inhibitors activated pulmonary macrophages and attenuated lung metastasis in vivo. These findings highlight the importance of CRP in lung metastasis, which may represent an effective therapeutic target for patients with advanced solid cancers in clinics.

中文翻译：

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C 反应蛋白通过激活肺巨噬细胞中的 FcγR2B 促进肺转移来诱导免疫抑制


C 反应蛋白 （CRP） 是一种肝源性急性期反应物，是与癌症预后不良相关的炎症的临床标志物。在许多类型的癌症中观察到 CRP 水平升高，并且与转移风险显着增加有关，表明 CRP 可能具有促转移作用。在这里，我们报道了 CRP 通过抑制乳腺癌和黑色素瘤中肺巨噬细胞的抗癌能力来促进肺转移。与野生型小鼠相比，小鼠 CRP 缺失抑制了乳腺癌和黑色素瘤细胞的肺转移，而不会显着影响肿瘤生长。此外，CRP 缺陷小鼠的肺中富集了活化的肺巨噬细胞，通过全身施用人 CRP，可以将其降低到野生型小鼠的水平。从机制上讲，CRP 以 FcγR2B 依赖性方式阻断共生菌诱导的肺巨噬细胞的激活，从而损害巨噬细胞介导的免疫监视，从而促进荷瘤小鼠肺部转移前生态位的形成。因此，用特异性 CRP 抑制剂治疗可激活肺巨噬细胞并减轻体内肺转移。这些发现强调了 CRP 在肺转移中的重要性，这可能代表临床晚期实体癌患者的有效治疗靶点。